Fight Aging!https://www.fightaging.org/
Reports from the front line in the fight against aging. The science of healthy life extension. Activism and advocacy for longer, healthier lives.http://creativecommons.org/licenses/by/3.0/en-usreason@fightaging.org2015-03-31T06:55:40-06:00https://www.fightaging.org/icon.pngFight Aging!https://www.fightaging.org/
daily12000-01-01T12:00+00:00More on Molecular Tweezers to Treat Amyloid Accumulationhttps://www.fightaging.org/archives/2015/03/more-on-molecular-tweezers-to-treat-amyloid-accumulation.php
Amyloids are misfolded proteins that gather to form solid aggregates in tissues. Their presence grows with age and some types of amyloid are known to contribute to the pathology of specific age-related conditions: amyloid-β in Alzheimer's disease and misfolded transthyretin in senile systemic amyloidosis for example. Any potential rejuvenation toolkit must include a reliable technology platform for clearance of the various forms of amyloid. Of late researchers have been working on the use of what they call molecular tweezers for this purpose, and seem to be making meaningful progress: An international team of more than 18 research groups has demonstrated...Amyloids are misfolded proteins that gather to form solid aggregates in tissues. Their presence grows with age and some types of amyloid are known to contribute to the pathology of specific age-related conditions: amyloid-β in Alzheimer's disease and misfolded transthyretin in senile systemic amyloidosis for example. Any potential rejuvenation toolkit must include a reliable technology platform for clearance of the various forms of amyloid. Of late researchers have been working on the use of what they call molecular tweezers for this purpose, and seem to be making meaningful progress:

An international team of more than 18 research groups has demonstrated that the compounds they developed can safely prevent harmful protein aggregation in preliminary tests using animals. The findings raise hope that a new class of drugs may be on the horizon for the more than 30 diseases and conditions that involve protein aggregation, including diabetes, cancer, spinal cord injury, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). Proteins are necessary for almost every cellular process. However, when cell machinery doesn't clear out old proteins, they can clump, or aggregate, into toxic plaques that lead to disease.

The researchers call the compounds that they developed molecular tweezers because of the way they wrap around the lysine amino acid chains that make up most proteins. The compounds are unique in their ability to attack only aggregated proteins, leaving healthy proteins alone. To develop a new drug, researchers typically screen large libraries of compounds to find ones that affect a protein involved in a disease. This team used a fundamentally different approach to develop the molecular tweezers. "We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping. Then, we developed a tailored solution. So unlike many other drugs, we understand how and why our drug works."

The team is in the process of testing multiple versions of the tweezers, each with a slightly different molecular makeup. For CLR01, one of the most promising versions, the researchers have demonstrated therapeutic benefits in two rodent models of Alzheimer's disease, two fish and one mouse model of Parkinson's disease, a fish model of spinal cord injury and a mouse model of familial amyloidotic polyneuropathy, a rare disease in which protein aggregation affects the nervous system, heart and kidneys. "Our data suggest that CLR01, or a derivative thereof, may become a drug for a number of diseases that involve protein aggregation. We also found a high safety window for CLR01." In one of the safety tests, mice receiving a daily CLR01 dose 250 times higher than the therapeutic dose for one month showed no behavioral or physiological signs of distress or damage. In fact, blood cholesterol in the mice dropped by 40 percent, a possible positive side effect of CLR01.

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11181@https://www.fightaging.org/ReasonDaily News2015-03-31T06:55:40-06:00Investigating Hibernation and Longevity in Lemurshttps://www.fightaging.org/archives/2015/03/investigating-hibernation-and-longevity-in-lemurs.php
There has been some interest in deeper investigations of metabolism and aging in mammals via the study of hibernating species. For any stable altered state of metabolism, such as the calorie restriction response or hibernation, a greater understanding of the mechanisms involved may shed light on a range of issues. In the case of hibernation there is a long way to go yet, however. Research is still in the early stages, and comparatively few scientists study hibernation with this perspective: The conventional wisdom in longevity research is that smaller species live shorter lives than larger ones. For example, humans and...There has been some interest in deeper investigations of metabolism and aging in mammals via the study of hibernating species. For any stable altered state of metabolism, such as the calorie restriction response or hibernation, a greater understanding of the mechanisms involved may shed light on a range of issues. In the case of hibernation there is a long way to go yet, however. Research is still in the early stages, and comparatively few scientists study hibernation with this perspective:

The conventional wisdom in longevity research is that smaller species live shorter lives than larger ones. For example, humans and whales can live to be over 100; yet the average lab mouse doesn't live beyond its third birthday. The researchers found an exception to this pattern in a group of hamster-sized lemurs with a physiological quirk - they are able to put their bodies in standby mode.

Researchers combed through more than 50 years of medical records on hundreds of dwarf lemurs and three other lemur species for clues to their exceptional longevity. How long the animals live and how fast they age correlates with the amount of time they spend in a state of suspended animation known as torpor, the data show. Hibernating lemurs live up to ten years longer than their non-hibernating cousins. Dwarf lemurs were the most extreme examples in their study, spending up to half the year in deep hibernation in the wild. Dwarf lemurs go into a semi-hibernation state for three months or less in captivity, but even that seems to confer added longevity.

Hibernating dwarf lemurs can reduce their heart rate from 200 to eight beats per minute. Breathing slows, and the animals' internal thermostat shuts down. Instead of maintaining a steady body temperature, they warm up and cool down with the outside air. For most primates such vital statistics would be life-threatening, but for lemurs, they're a way to conserve energy during times of year when food and water are in short supply. Hibernating lemurs not only live longer, they also stay healthier. While non-hibernators are able to reproduce for roughly six years after they reach maturity, hibernators continue to have kids for up to 14 years after maturity, the researchers found. Although all species they examined suffered from cataracts and other age-related eye diseases as they got older, the hibernators managed to stave off symptoms until much later in life.

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11180@https://www.fightaging.org/ReasonDaily News2015-03-31T06:40:34-06:00Living Longer and Aging More Slowlyhttps://www.fightaging.org/archives/2015/03/living-longer-and-aging-more-slowly.php
The old are not as physically aged as they used to be. Today's old people are in better shape than their predecessors, with access to better medicine and having been exposed to a lesser burden of infectious disease and other causes of cell and tissue damage over the course of a lifetime. Given the pace of progress in medical science these improvements can be seen even over the course of the past few decades. Many of today's researchers look at this and see compression of morbidity, a popular viewpoint in which it is believed that healthy life span can be...The old are not as physically aged as they used to be. Today's old people are in better shape than their predecessors, with access to better medicine and having been exposed to a lesser burden of infectious disease and other causes of cell and tissue damage over the course of a lifetime. Given the pace of progress in medical science these improvements can be seen even over the course of the past few decades. Many of today's researchers look at this and see compression of morbidity, a popular viewpoint in which it is believed that healthy life span can be extended considerably without extending overall life span. This doesn't make a great deal of sense from the viewpoint of aging as a consequence of accumulated biological damage, however. In the damage perspective the risk of death and level of dysfunction and frailty are determined by the present levels of various forms of damage. Reducing the pace at which the damage load increases extends both overall life span and time spent in decline; you can't have one without the other. Making an immediate reduction in damage, such as through some form of rejuvenation treatment, will extend healthy life span and postpone the future decline, but absent further treatments that decline would look exactly the same when it does arrive.

The only way in which you might see something that looks like compression of morbidity is if the pace of accumulation for most forms of damage are slowed, but not for one or more late-onset types of damage that produce reliably fatal consequences. This may or may not be what has happened over the past fifty years or so; there is a lot of room for argument given the present state of data. One intriguing line of thought relates to senile systemic amyloidosis, which seems to be the cause of death for most supercentenarians. It isn't much seen in less aged individuals, and there is comparatively little known of its progression in old age.

Still, the old are getting younger. Not fast enough yet, but step by step as a side-effect of improvements across the board in health, wealth, and medical science. The goal for the future is to step away from this incidental improvement in favor of strategies that deliberately target the causes of aging for treatment and repair. The coming age of medicine will prove to be far more effective in extending healthy life: there is a great deal of difference between trying and not trying to achieve a given goal.

Looking at two stages of the Berlin Aging Study, the first carried out between 1990 and 1993 and the second between 2013 and 2014, the team made some large-scale assessments of how old-age vitality has changed, along with some speculations as to why. Overall, despite growing obesity concerns and a stagnant international smoking rate, people seem to be aging more gracefully. Past the advances that have kept people in better physical shape, cognitive tests showed 75-year-olds today were an average of 19.6 years "younger" relative to 75-year-olds in the early 1990s. That is, people tested at 75 today performed as well as a 55-year-old would have two decades ago. "This is, by any means, a huge effect."

On average, today's 75-year-olds are cognitively much fitter than the 75-year-olds of 20 years ago. At the same time, the current generation of 75-year-olds also reports higher levels of well-being and greater life satisfaction. "The gains in cognitive functioning and well-being that we have measured here in Berlin are considerable and of great significance for life quality in old age." The researchers relate the gains to sociocultural factors such as education. In their opinion, the increase in well-being is also due to better physical fitness and higher levels of independence in old age. "However, we expect that these positive historical trends are attenuated at the end of life." During the final stage of life, the increase in good years of life is likely to give way to a rapid and marked drop in both cognition and well-being.

We compared data obtained 20 years apart in the Berlin Aging Study (BASE, in 1990-93) and the Berlin Aging Study II (BASE-II, in 2013-14). Relative to the earlier-born BASE cohort, the later-born BASE-II cohort showed better cognitive performance and reported higher well-being, presumably due to culture-based advances in the course of the past century. Our results suggest that historical trends favoring later-born cohorts in cognitive performance carry into old age, constitute strong effects at age 75 years, and generalize to multiple key indicators of perceived quality of life. The cognitive performance of BASE-II participants was on average 19.61 years "younger" relative to the BASE cohort.

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11179@https://www.fightaging.org/ReasonMedicine, Biotech, Research2015-03-30T15:30:40-06:00Fitness Versus Mortality after Cancer Diagnosishttps://www.fightaging.org/archives/2015/03/fitness-versus-mortality-after-cancer-diagnosis.php
A greater level of fitness in mid-life is shown in many large studies to correlate with improved health and greater life expectancy. The data from this study shows that increased fitness correlates with lower mortality from cardiovascular disease and some cancers in those patients with a cancer diagnosis in their medical history: Cardiorespiratory fitness (CRF) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases, but its association with incident cancer or survival following a diagnosis of cancer has received little attention. The study included 13 949 community-dwelling men who had a baseline fitness examination. All...A greater level of fitness in mid-life is shown in many large studies to correlate with improved health and greater life expectancy. The data from this study shows that increased fitness correlates with lower mortality from cardiovascular disease and some cancers in those patients with a cancer diagnosis in their medical history:

Cardiorespiratory fitness (CRF) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases, but its association with incident cancer or survival following a diagnosis of cancer has received little attention. The study included 13 949 community-dwelling men who had a baseline fitness examination. All men completed a comprehensive medical examination, a cardiovascular risk factor assessment, and incremental treadmill exercise test to evaluate CRF. We used age- and sex-specific distribution of treadmill duration from the overall Cooper Center Longitudinal Study population to define fitness groups as those with low (lowest 20%), moderate (middle 40%), and high (upper 40%) CRF groups. Cardiorespiratory fitness levels were assessed between 1971 and 2009, and incident lung, prostate, and colorectal cancer using Medicare claims data from 1999 to 2009; the analysis was conducted in 2014.

Compared with men with low CRF, the adjusted hazard ratios (HRs) for incident lung, colorectal, and prostate cancers among men with high CRF were 0.45, 0.56, and 1.22, respectively. Among those diagnosed as having cancer at Medicare age, high CRF in midlife was associated with an adjusted 32% risk reduction in all cancer-related deaths and a 68% reduction in cardiovascular disease mortality following a cancer diagnosis compared with men with low CRF in midlife. There is an inverse association between midlife CRF and incident lung and colorectal cancer but not prostate cancer. High midlife CRF is associated with lower risk of cause-specific mortality in those diagnosed as having cancer at Medicare age.

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11178@https://www.fightaging.org/ReasonDaily News2015-03-30T07:09:00-06:00Considering Alzheimer's Disease as a Type 3 Diabeteshttps://www.fightaging.org/archives/2015/03/considering-alzheimers-disease-as-a-type-3-diabetes.php
A number of researchers have pointed out similarities between some of the risk factors and mechanisms of type 2 diabetes and Alzheimer's disease, a few even going so far as to suggest that Alzheimer's should be classified as type 3 diabetes: Type 2 diabetes mellitus (T2DM) is currently extremely common due to the prevalence of obesity, as well as the aging of the population. Prevention and treatment strategies for the classical macrovascular and microvascular complications of diabetes mellitus have significantly improved. Therefore, people are living longer with diabetes mellitus, which might lead to the emergence of new complications. Dementia is...A number of researchers have pointed out similarities between some of the risk factors and mechanisms of type 2 diabetes and Alzheimer's disease, a few even going so far as to suggest that Alzheimer's should be classified as type 3 diabetes:

Type 2 diabetes mellitus (T2DM) is currently extremely common due to the prevalence of obesity, as well as the aging of the population. Prevention and treatment strategies for the classical macrovascular and microvascular complications of diabetes mellitus have significantly improved. Therefore, people are living longer with diabetes mellitus, which might lead to the emergence of new complications. Dementia is one example of these emerging new complications. Compared with the general population, the increased risk of dementia is 50%-150% in people with T2DM.

In this review, we discuss insulin resistance and deficiency. Studies have shown that insulin resistance and deficiency can interact with amyloid-β protein and tau protein phosphorylation, each leading to the onset and development of AD. Based on those epidemiological data and basic research, it was recently proposed that AD can be considered as "type 3 diabetes". Special attention has been paid to determining whether antidiabetic agents might be effective in treating AD. There has been much research both experimental and clinical on this topic. Although the results of these trials seem to be contradictory, this approach is also full of promise.